In this proposal we will examine whether neurons in the nucleus submedius (SM) of the rat medial thalamus play a role in nociception. Initially, we will focus on (1) an in vivo examination of physiological responses and neuropeptide-induced changes in excitability of SM neurons, and (2) an in vitro study of their morphological features, membrane properties and neuropeptide mechanism(s) of action. Preliminary experiments indicate that some SM neurons are activated by noxious stimuli. We would like to extend these observations, and perform a detailed analysis of SM neuronal properties by using single-unit recordings and a battery of cutaneous stimuli. Preliminary data additionally indicate the presence of enkephalin in the SM, and the possibility that calcitonin gene-related peptide might play a neurotransmitter role in the SM. We will examine the effects these neuropeptides have on physiologically characterized neurons when applied with the iontophoretic technique. We would also like to gain insights into the functional organization of the SM. We will thus perform a detailed morphological analysis of SM neurons using a computer-aided three- dimensional reconstruction system. Of special interest are neurons physiologically characterized and intracellularly injected with horseradish peroxidase in vivo, or cells identified as projecting to the frontal cortex or receiving input from trigeminal and spinal afferents and stained with Lucifer Yellow in vitro. Finally, we will use in vitro brain slices to examine the electrophysiological membrane properties of SM neurons (particularly those identified as projecting to the frontal cortex or receiving input in trigeminal or spinal afferents), and study the mechanism of action of enkephalin and calcitonin gene-related peptide on these cells. The proposal should increase our knowledge of nociception at spinal, trigeminal, thalamic and cortical levels, and this knowledge might lead to significant advances in dental and cutaneous pain management.